Expression of T cell immunoglobulin- and mucin-domain-containing molecules (TIMs) can be used as T helper (Th) differentiation markers in the human and mouse. We examined the expression of TIM-1 and -3 mRNAs in rat MBP(63-88)-induced experimental autoimmune encephalomyelitis (EAE). TIM-3 expression was upregulated in the spinal cord during EAE and following antigen restimulation of the encephalitogenic TCRBV8S2+ population. Interestingly, TIM-3 expression was also detected by in situ hybridization in resident cells of the nervous system. TIM-1 was expressed in B cells but not in resident CNS cells and TIM-1 mRNA levels in spinal cord were unchanged throughout the course of EAE. These results support the notion that TIM-3 can also be used as a Th1 differentiation marker in the rat. However, expression of TIM-1 and -3 is not restricted solely to T cells and the presence of TIM-3 in resident CNS cells may indicate a role for this molecule in the interaction between the nervous and immune systems.